Tolerability and Effectiveness of Definitive Chemoradiotherapy in Locally Advanced Lung Cancer Patients with Combined Pulmonary Fibrosis and Emphysema

Background This study evaluated the efficacy and safety of definitive chemoradiotherapy (CRT) for lung cancer in patients with combined pulmonary fibrosis and emphysema (CPFE), focusing on radiation pneumonitis (RP). Materials and Methods This retrospective cohort study included patients with locally advanced lung cancer treated with definitive CRT at Kishiwada City Hospital from 2014 to 2024. CPFE was defined as coexisting upper-lobe emphysema and lower-lobe fibrosis. Outcomes included RP incidence, progression-free survival (PFS), and overall survival (OS). Results Among 182 patients, 40 (22%) had CPFE. The incidence of grade ≥1 RP was comparable between the CPFE and non-CPFE groups (75% vs 81%, p = 0.41) with no significant difference in severity. Among patients with non-small cell lung cancer, the CPFE group exhibited shorter PFS and OS than the non-CPFE group (median PFS: 10 vs. 19 months, p = 0.01; median OS: 13 vs. 70 months, p < 0.01; respectively). However, among those who received durvalumab, PFS was comparable between the CPFE and non-CPFE groups (hazard ratio, 1.41; 95% confidence interval 0.69–2.90). Among patients with small cell lung cancer (n = 42), the CPFE and non-CPFE groups exhibited comparable PFS (median 11 vs. 12 months, p = 0.43), although the CPFE group exhibited a trend for shorter OS (median 23 vs. 34 months, p = 0.05). Conclusion Definitive CRT did not increase RP risk in patients with CPFE. Despite poorer prognosis, CRT, particularly when followed by durvalumab, might serve as a feasible and beneficial therapeutic approach for CPFE-associated lung cancer.